Clonal selection in the human Vδ1 T cell repertoire indicates γδ TCR-dependent adaptive immune surveillance.
Clonal selection in the human Vδ1 T cell repertoire indicates γδ TCR-dependent adaptive immune surveillance.
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DOI：
10.1038/ncomms14760
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发表时间：
2017-03-01
影响因子：
16.6
通讯作者：
Willcox BE
中科院分区：
文献类型：
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作者：
Davey MS;Willcox CR;Joyce SP;Ladell K;Kasatskaya SA;McLaren JE;Hunter S;Salim M;Mohammed F;Price DA;Chudakov DM;Willcox BE
γδ T细胞被认为是先天样淋巴细胞，对应激反应迅速，没有克隆选择和分化。在这里，我们使用下一代测序来探索这种模式如何与人类Vδ2neg T细胞相关，涉及对病毒感染和癌症的反应。流行的Vδ1 T细胞受体（TCR）库是私有的，最初在脐带血中不集中，到成年期通常会强烈集中在一些高频克隆型上。克隆扩增已从与CD27下调相关的幼稚表型分化为效应表型，保留增殖能力和TCR敏感性，显示细胞毒性标记物增加和归巢能力改变，并随着时间的推移保持相对稳定。相比之下，Vδ2+ T细胞表达半不变的tcr，这种tcr在出生时就存在，并在个体之间共享。因此，人类Vδ1+ T细胞从Vδ2+亚群进化出了一种独特的生物学，涉及到γδ TCR在指导一种高度适应性但非常规的免疫监视形式中的核心、个性化作用。γδ T细胞通常被认为是先天样淋巴细胞。本文作者对人γδ T细胞受体（TCR）进行了测序，以显示Vδ1 TCR库的聚焦，这表明与Vδ2 T细胞不同，Vδ1 T细胞区室具有适应性属性。
γδ T cells are considered to be innate-like lymphocytes that respond rapidly to stress without clonal selection and differentiation. Here we use next-generation sequencing to probe how this paradigm relates to human Vδ2neg T cells, implicated in responses to viral infection and cancer. The prevalent Vδ1 T cell receptor (TCR) repertoire is private and initially unfocused in cord blood, typically becoming strongly focused on a few high-frequency clonotypes by adulthood. Clonal expansions have differentiated from a naive to effector phenotype associated with CD27 downregulation, retaining proliferative capacity and TCR sensitivity, displaying increased cytotoxic markers and altered homing capabilities, and remaining relatively stable over time. Contrastingly, Vδ2+ T cells express semi-invariant TCRs, which are present at birth and shared between individuals. Human Vδ1+ T cells have therefore evolved a distinct biology from the Vδ2+ subset, involving a central, personalized role for the γδ TCR in directing a highly adaptive yet unconventional form of immune surveillance. γδ T cells are generally considered innate-like lymphocytes. Here the authors sequence human γδ T cell receptors (TCR) to show focusing of the private Vδ1 TCR repertoire, suggesting that, unlike Vδ2 T cells, the Vδ1 T cell compartment has adaptive attributes.